Injuries to the central nervous system (CNS) are among the most devastating and costly of human afflictions. Recent advances in science and technology now provide tools which, for the first time, permit methodical approaches to repair or regenerate damaged CNS axons. Such tools include, among others, a variety of neurotrophic and signaling factors, cell adhesion molecules, disinhibiting agents, cell and gene-based therapies, and reliable animal models of neurotrama. Several laboratories have reported encouraging progress in applying such interventions to enhance axonal regeneration and functional recovery following CNS injury. A key challenge in the development of such therapies is the application of potent bioactive factors that promote nerve regeneration in vivo. L1 is a neuronal cell adhesion molecule (CAM) that is a potent promoter of axonal growth in culture. Phase I of this grant proposes to synthesize fragments of human L1 as Fc fusion proteins and test their ability to promote neurite outgrowth in culture. The L1 fusion proteins will then be tested for functional recovery in a model for acute spinal cord injury in the rat. The Phase I studies are preparatory to a Phase II program in which we will systematically evaluate the activities of various forms of human L1-Fc, optimize the dosage of these molecules in vivo, and explore the efficacy of L1-Fc in a model for chronic spinal cord injury. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE